Caveolin-3 is involved in the protection of resveratrol against high-fat-diet-induced insulin resistance by promoting GLUT4 translocation to the plasma membrane in skeletal muscle of ovariectomized rats
Caveolin-3 is involved in the protection of resveratrol against high-fat-diet-induced insulin resistance by promoting GLUT4 translocation to the plasma membrane in skeletal muscle of ovariectomized rats
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Caveolin-3 通过促进 GLUT4 易位至卵巢切除大鼠骨骼肌质膜，参与白藜芦醇对抗高脂饮食诱导的胰岛素抵抗的保护
DOI：
10.1016/j.jnutbio.2011.12.003
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发表时间：
2012-12-01
影响因子：
5.6
通讯作者：
Wang, Ting-Huai
中科院分区：
文献类型：
--
作者：
Tan, Zhi;Zhou, Li-Jun;Wang, Ting-Huai
胰岛素抵抗被认为是一种常见的代谢因素，可预测 2 型糖尿病和动脉粥样硬化疾病的未来发展。白藜芦醇 (RSV) 是一种雌激素受体 (ER) 激动剂，已知会影响胰岛素敏感性，但其机制尚不清楚。有证据表明，caveolin-3 (CAV-3) 是 Caveolin 家族的成员，参与胰岛素刺激的葡萄糖摄取。我们最近的研究表明，雌激素通过 ER 上调 CAV-3 表达来改善葡萄糖摄取。在这里，我们在体内和体外研究了 CAV-3 在 RSV 对骨骼肌胰岛素抵抗的影响中的作用。结果表明，RSV 可改善卵巢切除大鼠中高脂饮食 (HFD) 诱导的葡萄糖耐受不良和胰岛素抵抗。 RSV 通过增强 GLUT4 易位到质膜而不是增加 GLUT4 蛋白表达来增加体内离体比目鱼肌和体外 C2C12 肌管中胰岛素刺激的葡萄糖摄取。通过 ER α 介导的转录，RSV 增加了 CAV-3 蛋白的表达，从而导致 GLUT4 易位。此外，敲除CAV-3基因后，RSV对葡萄糖摄取和GLUT4易位到质膜以及CAV-3和GLUT4在膜中的结合的影响显着减弱。我们的研究结果表明，RSV 通过 ER α 传播。 CAV-3表达升高，然后增强GLUT4向质膜的易位，促进骨骼肌葡萄糖摄取，发挥其对HFD诱导的胰岛素抵抗的保护作用。这表明该通路可能是对抗 HFD 引起的胰岛素抵抗综合征的有效治疗靶点。 (C) 2012 Elsevier Inc. 保留所有权利。
Insulin resistance is recognized as a common metabolic factor which predicts the future development of both type 2 diabetes and atherosclerotic disease. Resveratrol (RSV), an agonist of estrogen receptor (ER), is known to affect insulin sensitivity, but the mechanism is unclear. Evidence suggests that caveolin-3 (CAV-3), a member of the caveolin family, is involved in insulin-stimulated glucose uptake. Our recent work indicated that estrogen via ER improves glucose uptake by up-regulation of CAV-3 expression. Here, we investigated the role of CAV-3 in the effect of RSV on insulin resistance in skeletal muscle both in vivo and in vitro. The results demonstrated that RSV ameliorated high-fat-diet (HFD)-induced glucose intolerance and insulin resistance in ovariectomized rats. RSV elevated insulin-stimulated glucose uptake in isolated soleus muscle in vivo and in C2C12 myotubes in vitro by enhancing GLUT4 translocation to the plasma membrane rather than increasing GLUT4 protein expression. Through ER alpha-mediated transcription, RSV increased CAV-3 protein expression, which contributed to GLUT4 translocation. Moreover, after knockdown of CAV-3 gene, the effects of RSV on glucose uptake and the translocation of GLUT4 to the plasma membrane, as well as the association of CAV-3 and GLUT4 in the membrane, were significantly attenuated. Our findings demonstrated that RSV via ER alpha. elevated CAV-3 expression and then enhanced GLUT4 translocation to the plasma membrane to promote glucose uptake in skeletal muscle, exerting its protective effects against HFD-induced insulin resistance. It suggests that this pathway could represent an effective therapeutic target to fight against insulin resistance syndrome induced by HFD. (C) 2012 Elsevier Inc. All rights reserved.